Formation of covalent adducts between cortisol and 16 alpha-hydroxyestrone and protein: possible role in the pathogenesis of cortisol toxicity and systemic lupus erythematosus.
The incubation of albumin with cortisol or 16 alpha-hydroxyestrone results in the formation of covalent steroid-protein adducts. The rate of adduct formation increases in the presence of sodium cyanoborohydride (NaCNBH3), indicating that the reaction proceeds nonenzymatically through a Schiff base intermediate. Under nonreducing conditions, a stable adduct forms with cortisol and 16 alpha-hydroxyestrone but not with estrone, which lacks a hydroxyl group adjacent to the reactive carbonyl. It is hypothesized that a Heyns rearrangement involving the adjacent hydroxyl group traps the Schiff base and produces a stable ketoamine adduct. The binding of 16 alpha-hydroxyestrone and cortisol to albumin is significantly inhibited by acetylsalicylic acid, which has been shown to acetylate an epsilon-amino group of a lysine residue in albumin. High-pressure liquid chromatography analysis of an acid hydrolysate of 16 alpha-hydroxyestrone-albumin shows that a product containing 16 alpha-hydroxyestrone coelutes with a standard prepared by reacting 16 alpha-hydroxyestrone with the epsilon-amino group of lysine. We propose that the formation of covalent steroid-protein adducts is a generalized phenomenon which may contribute to the pathological effects produced by elevated levels of certain endogenous steroids.
D000107:Acetylation; D055598:Chemical Phenomena; D002621:Chemistry; D004970:Estrone / Q000031:analogs & derivatives; D006854:Hydrocortisone / Q000633:toxicity; D006894:Hydroxyestrones; D008180:Lupus Erythematosus, Systemic / Q000209:etiology; D008239:Lysine; D012709:Serum Albumin
D006894:Hydroxyestrones; D012709:Serum Albumin; C026702:16-hydroxyestrone; D004970:Estrone; D008239:Lysine; D006854:Hydrocortisone